The Effect Of Perinatal BPA Exposure On Kidney Toxicity In The Rat Offspring

Objective: Bisphenol A (BPA)，one of the typical EDDs, was mainly for the production ofpolycarbonate, epoxy resin, polysulfone resin, polyphenylene ether resin, unsaturatedpolyester resins and other polymer materials. Its widespread use has caused seriouspollution to the environment，and represented serious threat to the health of the populationof almost every country in the world. Previous studies have shown sub-acute exposure tobisphenol A, had caused kidney damage and hydronephrosis in juvenile male rats. However,whether perinatal BPA exposure causes renal damage in rat offspring a not clear.This studyused a rat model to study the impact of perinatal exposure to BPA on kidneys of offspringrats.Methods: Throughout pregnancy and lactation，pregnant Wistar rats were administeredcorn oil,50,250μg/kg/day BPA by oral gavage. After weaning, offspring were accepted aconventional diet of15weeks. The body weight and other physiological changes weremonitored. After the collection of urine, each group of offspring at15weeks weresacrificed，and the kidneys and other major organs were collected，With the biochemicalanalyzer、hematoxylin-eosin staining、Masson staining、Real-time PCR、western blottingand Immunohistochemical techniques, the biochemical indicators such as urinary creatinine,blood urea nitrogen, and urine total protein. pathological changes of kidney， thehydronephrosis fibrosis-related molecules such as TGF-beta1、 Smad2、VEGF、EGF、ET-1, CD40、CD3and type IV collagen mRNA levels and protein levels were detected.Resμlts: During lactation, compared with the control, body weight of each dose group ofoffspring was no different. From weaning to sacrificing at15weeks, there were no difference in the body weight，kidney weight and kidney coefficient in female offspring.The body weight of male offspring in each dose group was increased compared withcontrols. The kidney weight and kidney coefficient of male offspring in each dose group on15weeks of age got the decreasing trend, but with no significant difference. There were nosignificant different in UPE、 BUN and CR in female offspring in each dosegroup.Compared with control group, the UPE and Cr of male offspring were significantlyincreased, while there was no statistically significance in BUN between each dose groupand control group; Compared with the control, slices for the kidney of male offspring ineach dose group showed a certain pathological changes, such as thinner renal parenchymal,wider renal interstitial substance, expansed renal tubule, damaged structure of part of theglomerula, and losing normal morphology, with cell infiltration. The expression mRNA ofTGF-β1and its downstream signal molecules--Smad2was increased, and that of VEGFwas significantly decreased, which were also verified with Western blot. The ET-1mRNAexpression in low-dose group, were significantly higher. Immunohistochemical resultsshowed that bquality of CD3+T lymphocytes of renal interstitium in low dose group wassiginificantly increased, and the CD40expression in renal tubular epithelial cell in the lowdose group of was also significantly enhanced. The collagen of type IV in renal tubularepithelial cells and basement membrane in male offspring were positive expression.Conclusion: Perinatal (50μg/kg/day,250μg/kg/day) BPA exposure can cause kidneyfunction damage, hydronephrosis and fibrosis-like changes in male rat offspring with adose-dependent manner.